A2PE*H2 is a secondary irreversible photochemical product generated during periods of high alltrans- etinal generation (i.e., receptor photopigment bleaching) in the retinal photoreceptor outer segments. It has an absorption maximum at 505nm and emits fluorescence peaked at 620nm. Dr. Bonner has hypothesized that the increasing A2E levels with age are cytotoxic to the RPE cells when internal stores within the secondary lysosomes reach too high a level and the rate at which A2E leaches from these granules exceeds the rate at which endoplasmic reticulum reprocessing segregates A2E back into the granules. The induced RPE dysfunction is the earliest and potentially reversible stage of age-related macular degeneration, the most common cause of blindness in affluent societies. In this SGER a cross-disciplinary approach is taken to develop spectral image analysis techniques suitable for extracting the retinal distribution maps of the different fluorescent molecules in the A2E pathway from a series of noninvasive spectral images of macular autofluorescence. If this grant is successful, then clinical studies can be applied by these techniques to test the theory that the role of spectral imbalance in AMD progression and to evaluate disease prevention strategies based on spectrally modifying A2E production and photo-oxidation rates.
